Epstein-Barr virus (EBV) raises the risk of developing seven different types of autoimmune disease—including type 1 diabetes (T1D)—according to a recent study published in Nature Genetics.

“Now, using genomic methods that were not available 10 years ago, it appears that components made by the virus interact with human DNA in the places where the genetic risk of disease is increased,” said lead author John B. Harley, MD, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. “And not just for lupus, but for all these other diseases, too.”

Epstein-Barr virus has been linked to the autoimmune mechanisms of systemic lupus erythematous (SLE), with the virus increasing SLE risk in children up to 50 times. Furthermore, patients with SLE have increased EBV levels in the blood and early lytic viral gene expression. Regardless of proposed ties between EBV and autoimmune diseases like SLE, however, a fundamental mechanism explaining such associations has yet to be discovered.

Germline DNA polymorphisms likely alter SLE risk based on results from genome-wide association studies, which have identified more than 50 SLE susceptibility loci. These susceptibility loci mostly lie in gene regulatory regions.

“We therefore asked whether any of the DNA-interacting proteins encoded by EBV preferentially bind SLE risk loci,” the researchers wrote. “Our analyses identified strong associations with an EBV gene product (EBNA2), providing a potential origin of gene-environment interaction, along with a set of human transcription factors and cofactors (TFs), in SLE and six other autoimmune diseases.”

The researchers identified TFs that bind risk loci for individual diseases using two novel algorithms developed at Cincinnati Children’s Hospital Medical Center during the course of several years.

Researchers found that EBV gene product EBNA2 and human TFs bind to a number of autoimmune risk loci representing SLE, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, and Type 1 Diabetes.

They suggest that gene action at select loci present in several autoimmune diseases occur at the level of the B cell, and propose that EBV EBNA2 TF alters how infected B cells function and interact with the body.

“These results offer promise for the development of future therapies for manipulating the action of these proteins in individuals harboring risk alleles at EBNA2-bound loci,” wrote the researchers.

Currently, at least one available drug can target 4 of the leading 20 high-risk TFs that co-occupy EBNA2 disorder loci with EBNA2. These findings also support fledgling efforts to develop an EBV vaccine. “This discovery is probably fundamental enough that it will spur many other scientists around the world to reconsider this virus in these disorders,” said Dr. Harley. “As a consequence, and assuming that others can replicate our findings, that could lead to therapies, ways of prevention, and ways of anticipating disease that don’t now exist.”

To read more about this study, click here.